The human heart consists of four valves, namely the mitral valve, tricuspid valve, pulmonary valve, and aortic valve, which can become damaged or diseased. According to statistics for 2005 published by the American Heart Association (AHA), valvular-related heart disease accounted for 20,891 mortalities (43,900 total mention mortalities), aortic valve disorder accounted for 13,137 mortalities (27,390 total mention mortalities), pulmonary valve disorder: accounted for 20 mortalities (45 total mention mortalities), mitral valve disorder accounted for 2,605 mortalities (6,210 total mention mortalities), tricuspid valve disorder accounted for 20 mortalities (114 total mention mortalities), and endocarditis accounted for 5,109 mortalities (10,120 total mention mortalities). Prosthetic heart valves have been used to replace such damaged or diseased heart valves. Of the four valves, the aortic valve experiences the largest day-to-day stress of any component of the heart, opening about 70 times a minute, or about 100,000 times a day. Accordingly, day-to-day stresses as well as additional stresses deriving from conditions or pathologies such as endocarditis, stenosis (restricted valve opening), or regurgitation (valve leakage), can ultimately accelerate improper valve function, particularly the aortic valve. If such conditions and stresses are left untreated, they can lead to heart failure. Currently, the end-stage treatment of dysfunctional heart valves, such as the aortic valve, involves replacement with a mechanical or a bioprosthetic device. While these mechanical and bioprosthetic heart valves have been used widely (the AHA estimates that 95,000 inpatient valve procedures were performed in 2003) they have certain disadvantages.
Mechanical valves are the most commonly and widely used prostheses. They are commonly made of titanium, cobalt-chromium alloy (Haynes 25), or pyrolytic carbon (Pyrolite). Compared to animal-derived heart valves, mechanical heart valves are more reliable and longer-lived (10-15 years with re-operation rates around 2-5%). Nevertheless, mechanical heart valves cause thrombus formation and calcification, which require that the patient maintains an anticoagulation therapeutic regimen for the rest of his or her life. Anticoagulation therapy has been linked to bleeding and other complications, such as damage of the red blood cells. It also predisposes the recipient to lifelong risks of infection.
Bioprosthetic valves are obtained from either animal origins (porcine valve or bovine pericardial valves) or human donors (cadavers). Animal-derived prostheses (stented and non-stented) use glutaraldehyde as a cross-linking agent, which enhances the mechanical stability of the prosthesis, but also fixes the protein configuration. This ultimately prevents cells in the prosthesis from growing, repairing and remodeling. Glutaraldehyde crosslinks have also been implicated as foci for calcification, which causes the prosthesis to deteriorate over time. Typically, bioprosthetic heart valve needs to be replaced within 5-15 years, depending on the age of the recipient. Immunologic reactions have also been noted with animal-based valve prosthesis, further limiting their use as a suitable substitute. The risk of transferring infectious diseases, such as zoonoses and Creutzfeldt-Jakob, to the patient also exists with the animal-derived prosthesis.
Human-derived aortic valves are obtained from cadavers. Although the aortic valve replacement with an allograft is ideal (because there is resistance to infection, no requirement for anticoagulation therapy, and surgical advantages) there are not enough human donors available. Cryopreserved pulmonary valves have been used to replace aortic valves but they can result in early failure. These valves also demonstrate gross regurgitation in vitro and are less robust against the hemodynamic stresses in the aortic position. Further, there is no consensus concerning the extent of cell viability within these human aortic valves.
Polymeric heart valves were first developed and sporadically used in clinics in 1950s but their use ceased soon thereafter because of high rates of thrombosis and thromboembolic complications and valve degeneration. However, in recent years, with the availability of new flexible polymers with improved biocompatibility, hemocompatibility and durability, polymer heart valves have regained considerable attention. Polyetherurethane, polyetherurethane urea, segmented polyurethanes, polycarbonate urethane, polyurethane valves coated with polyethylene oxide-grafted polyurethane, and polystyrene-b-polyisobutylene-polystyrene are among the polymers that show promise. The advantage of flexible polymer heart valves is that they can be fabricated into the native valve geometry and as a result they display normal hemodynamic function. The long term durability and hemodynamic function of these valves in vivo, however, remain to be proven. Thus, the search for a new material with improved performance continues.
Accordingly, there exists a need in the art for replacement heart valves that exhibit improved characteristics relative to existing mechanical and bioprosthetic heart valves.